Superior Diagnostic Yield of EBUS-Guided Cryobiopsy over Needle Aspiration in Isolated, Mass-Negative Mediastinal...

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard minimally invasive technique for mediastinal lymph node sampling; however, its diagnostic performance is limited in diseases requiring preserved tissue architecture, such as lymphoma and granulomatous disorders. EBUS-guided transbronchial mediastinal cryobiopsy (EBUS-TBMC) has emerged as a technique capable of obtaining larger, histologically intact samples. Evidence comparing these modalities in isolated mediastinal lymphadenopathy is limited. Methods: In this prospective, single-center, head-to-head cohort study, 89 consecutive patients with isolated mediastinal lymphadenopathy without parenchymal lung masses were enrolled. All patients underwent sequential EBUS-TBNA followed by EBUS-TBMC within the same session. The primary outcome was diagnostic yield; secondary outcomes included tissue adequacy and procedure-related complications. Results: EBUS-TBMC demonstrated a significantly higher diagnostic yield than EBUS-TBNA (83.1% vs. 28.0%, p < 0.001). TBMC established a diagnosis in 74/89 patients, whereas TBNA was diagnostic in 25/89. TBMC provided an additional diagnosis in 49 patients with non-diagnostic TBNA, while no case was diagnosed exclusively by TBNA. Superiority was consistent across malignant and benign conditions, particularly lymphoma and granulomatous diseases. Diagnostic yield was higher when ≥3 cryobiopsy samples were obtained (86.6% vs. 42.8%). Bleeding events were more frequent with TBMC but were mild-to-moderate, managed bronchoscopically, and no major complications or life-threatening events occurred. Conclusions: In isolated, mass-negative mediastinal lymphadenopathy, EBUS-TBMC provides a substantially higher diagnostic yield than TBNA. Early integration of TBMC may improve diagnostic efficiency and reduce the need for repeat or surgical procedures.